Cosmetic fixes

inst/templates/quarto/cpsr_classification.qmd

@@ -76,17 +76,14 @@ formula_gnomad <- as.formula(paste0("~", rlang::sym(tag_gnomad)))
 ### Pathogenic
 
    *  A total of __N = `r tot_variants[['class5']][['ClinVar']]`__ variants are registered with a <i>Pathogenic</i> clinical significance in the [ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/) database.
-   *  A total of __N = `r tot_variants[['class5']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Pathogenic</i> clinical significance by CPSR (refined ACMG criteria - based on population frequency and variant effect).
+   *  A total of __N = `r tot_variants[['class5']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Pathogenic</i> clinical significance by CPSR (refined ACMG/AMP criteria - based on population frequency and variant effect).
 
-::: {.callout-note}
-
-## Note - output limitations
+::: {.callout-note title="Note - output limitations"}
 
 In order to maintain responsiveness of client-side data interaction, variants displayed here constitute the top 2,000 variants for each of the ClinVar and non-ClinVar variant sets.
 
 :::
 
-
 <br>
 
 ::: {.panel-tabset}
@@ -227,7 +224,7 @@ crosstalk::bscols(
     crosstalk::filter_select("SYMBOL", "Gene", variants_class5_2, ~SYMBOL)
   ),
   list(
-    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG criteria codes)", variants_class5_2, ~CPSR_CLASSIFICATION_CODE),
+    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG/AMP criteria codes)", variants_class5_2, ~CPSR_CLASSIFICATION_CODE),
     crosstalk::filter_slider("CPSR_PATHOGENICITY_SCORE", "CPSR pathogenicity score", variants_class5_2, ~CPSR_PATHOGENICITY_SCORE, step = 0.5, ticks = T),
     crosstalk::filter_slider(tag_gnomad, paste0("MAF gnomAD (", desc_gnomad, ")"), variants_class5_2, formula_gnomad, sep = "", ticks = F)
   )
@@ -264,15 +261,15 @@ htmltools::br()
 ### Likely Pathogenic
 
 *  A total of __N = `r tot_variants[['class4']][['ClinVar']]`__ variants are recorded with a <i>Likely Pathogenic</i> clinical significance in the [ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/) database.
-*  A total of __N = `r tot_variants[['class4']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Likely Pathogenic</i> clinical significance by CPSR (refined ACMG criteria - based on population frequency and variant effect).
+*  A total of __N = `r tot_variants[['class4']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Likely Pathogenic</i> clinical significance by CPSR (refined ACMG/AMP criteria - based on population frequency and variant effect).
 
-::: {.callout-note}
+::: {.callout-note title="Note - output limitations"}
 
 In order to maintain responsiveness of client-side data interaction, variants displayed here constitute the top 2,000 variants for each of the ClinVar and non-ClinVar variant sets.
 
 :::
 
-<br><br>
+<br>
 
 ::: {.panel-tabset}
 
@@ -428,7 +425,7 @@ crosstalk::bscols(
     crosstalk::filter_select("SYMBOL", "Gene", variants_class4_2, ~SYMBOL)
   ),
   list(
-    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG criteria codes)", variants_class4_2, ~CPSR_CLASSIFICATION_CODE),
+    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG/AMP criteria codes)", variants_class4_2, ~CPSR_CLASSIFICATION_CODE),
     crosstalk::filter_slider("CPSR_PATHOGENICITY_SCORE", "CPSR pathogenicity score", variants_class4_2, ~CPSR_PATHOGENICITY_SCORE, step = 0.5, ticks = T),
     crosstalk::filter_slider(tag_gnomad, paste0("MAF gnomAD (", desc_gnomad, ")"), variants_class4_2, formula_gnomad, sep = "", ticks = F)
   )
@@ -473,15 +470,15 @@ htmltools::br()
 ### Variants of Uncertain Significance (VUS)</b>
 
 *  A total of __N = `r tot_variants[['class3']][['ClinVar']]`__ variants are recorded with a <i>VUS</i> clinical significance in the [ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/) database.
-*  A total of __N = `r tot_variants[['class3']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>VUS</i> clinical significance by CPSR (refined ACMG criteria - based on population frequency and variant effect).
+*  A total of __N = `r tot_variants[['class3']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>VUS</i> clinical significance by CPSR (refined ACMG/AMP criteria - based on population frequency and variant effect).
 
-::: {.callout-note}
+::: {.callout-note title="Note - output limitations"}
 
 In order to maintain responsiveness of client-side data interaction, variants displayed here constitute the top 2,000 variants for each of the ClinVar and non-ClinVar variant sets.
 
 :::
 
-<br><br>
+<br>
 
 ::: {.panel-tabset}
 
@@ -633,7 +630,7 @@ crosstalk::bscols(
   list(
     crosstalk::filter_select("miRNA_TARGET_HIT", "miRNA target gain/loss", variants_class3_2, ~miRNA_TARGET_HIT),
     crosstalk::filter_select("TF_BINDING_SITE_VARIANT", "TF binding site alteration", variants_class3_2, ~TF_BINDING_SITE_VARIANT),
-    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG criteria codes)", variants_class3_2, ~CPSR_CLASSIFICATION_CODE),
+    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG/AMP criteria codes)", variants_class3_2, ~CPSR_CLASSIFICATION_CODE),
     crosstalk::filter_slider("CPSR_PATHOGENICITY_SCORE", "CPSR pathogenicity score", variants_class3_2, ~CPSR_PATHOGENICITY_SCORE, step = 0.5, ticks = T),
     crosstalk::filter_slider(tag_gnomad, paste0("MAF gnomAD (", desc_gnomad, ")"), variants_class3_2, formula_gnomad, sep = "", ticks = F)
   )
@@ -678,15 +675,15 @@ htmltools::br()
 ### Likely Benign
 
 *  A total of __N = `r tot_variants[['class2']][['ClinVar']]`__ variants are recorded with a <i>Likely Benign</i> clinical significance in the [ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/) database.
-*  A total of __N = `r tot_variants[['class2']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Likely Benign</i> clinical significance by CPSR (refined ACMG criteria - based on population frequency and variant effect).
+*  A total of __N = `r tot_variants[['class2']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Likely Benign</i> clinical significance by CPSR (refined ACMG/AMP criteria - based on population frequency and variant effect).
 
-::: {.callout-note}
+::: {.callout-note title="Note - output limitations"}
 
 In order to maintain responsiveness of client-side data interaction, variants displayed here constitute the top 2,000 variants for each of the ClinVar and non-ClinVar variant sets.
 
 :::
 
-<br><br>
+<br>
 
 ::: {.panel-tabset}
 
@@ -829,7 +826,7 @@ crosstalk::bscols(
     crosstalk::filter_select("SYMBOL", "Gene", variants_class2_2, ~SYMBOL)
   ),
   list(
-    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG criteria codes)", variants_class2_2, ~CPSR_CLASSIFICATION_CODE),
+    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG/AMP criteria codes)", variants_class2_2, ~CPSR_CLASSIFICATION_CODE),
     crosstalk::filter_slider("CPSR_PATHOGENICITY_SCORE", "CPSR pathogenicity score", variants_class2_2, ~CPSR_PATHOGENICITY_SCORE, step = 0.5, ticks = T),
     crosstalk::filter_slider(tag_gnomad, paste0("MAF gnomAD (", desc_gnomad, ")"), variants_class2_2, formula_gnomad, sep = "", ticks = F)
   )
@@ -864,15 +861,15 @@ htmltools::br()
 ### Benign
 
 *  A total of __N = `r tot_variants[['class1']][['ClinVar']]`__ variants are recorded with a <i>Benign</i> clinical significance in the [ClinVar](https://www.ncbi.nlm.nih.gov/clinvar/) database.
-*  A total of __N = `r tot_variants[['class1']][['CPSR_ACMG']]`__ <i><b>Other</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Benign</i> clinical significance by CPSR (refined ACMG criteria - based on population frequency and variant effect).
+*  A total of __N = `r tot_variants[['class1']][['CPSR_ACMG']]`__ <i><b>non-ClinVar</b></i> variants (i.e. not submitted to/recorded in ClinVar) are classified with a <i>Benign</i> clinical significance by CPSR (refined ACMG/AMP criteria - based on population frequency and variant effect).
 
-::: {.callout-note}
+::: {.callout-note title="Note - output limitations"}
 
 In order to maintain responsiveness of client-side data interaction, variants displayed here constitute the top 2,000 variants for each of the ClinVar and non-ClinVar variant sets.
 
 :::
 
-<br><br>
+<br>
 
 ::: {.panel-tabset}
 
@@ -1014,7 +1011,7 @@ crosstalk::bscols(
     crosstalk::filter_select("SYMBOL", "Gene", variants_class1_2, ~SYMBOL)
   ),
   list(
-    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG criteria codes)", variants_class1_2, ~CPSR_CLASSIFICATION_CODE),
+    crosstalk::filter_select("CPSR_CLASSIFICATION_CODE", "CPSR classification (ACMG/AMP criteria codes)", variants_class1_2, ~CPSR_CLASSIFICATION_CODE),
     crosstalk::filter_slider("CPSR_PATHOGENICITY_SCORE", "CPSR pathogenicity score", variants_class1_2, ~CPSR_PATHOGENICITY_SCORE, step = 0.5, ticks = T),
     crosstalk::filter_slider(tag_gnomad, paste0("MAF gnomAD (", desc_gnomad, ")"), variants_class1_2, formula_gnomad, sep = "", ticks = F)
   )

inst/templates/quarto/cpsr_documentation.qmd

@@ -15,10 +15,10 @@ This report is intended for interpretation of inherited DNA variants implicated
 
 The variant interpretation procedures performed in this cancer genome report are relying upon multiple tools and knowledge resources, as outlined below. 
 
-::: {.callout-important}
-## Licensing note
+::: {.callout-important title="Licensing note"}
 
 Some resources (highlighted below) demand specific licensing agreements if you plan to utilize their data (and thus this report) in a commercial, non-research setting.
+
 :::
 
 
@@ -82,13 +82,13 @@ for(i in 1:NROW(ref_datasets)){
 
 ```
 
-### Variant classification algorithm (ACMG-based)
+### Variant classification algorithm (ACMG/AMP-based)
 
 <br>
 
-All coding, <b>non-ClinVar</b> variants in the set of cancer predisposition genes have been classified according to a <i>five-level pathogenicity scheme</i> (coined <b>CPSR_CLASSIFICATION</b> in the tables above). The scheme has the same five levels as those employed by ClinVar, e.g. pathogenic/likely pathogenic/VUS/likely benign/benign. The classification performed by CPSR is rule-based, implementing refined ACMG criteria, many of which were outlined in [SherLoc](https://www.invitae.com/en/variant-classification/) ([Nykamp et al., Genetics in Medicine, 2017](https://www.ncbi.nlm.nih.gov/pubmed/28492532)). Important attributes of cancer predisposition genes, such as mode of inheritance and mechanism of disease (loss-of-function), have been harvested from [Genomics England PanelApp](https://panelapp.genomicsengland.co.uk/), [Maxwell et al., Am J Hum Genet, 2016](https://www.ncbi.nlm.nih.gov/pubmed/27153395), and [Huang et al., Cell, 2018](https://www.ncbi.nlm.nih.gov/pubmed/29625052)
+All coding, <b>non-ClinVar</b> variants in the set of cancer predisposition genes have been classified according to a <i>five-level pathogenicity scheme</i> (coined <b>CPSR_CLASSIFICATION</b> in the tables above). The scheme has the same five levels as those employed by ClinVar, e.g. pathogenic/likely pathogenic/VUS/likely benign/benign. The classification performed by CPSR is rule-based, implementing refined ACMG/AMP criteria, many of which were outlined in [SherLoc](https://www.invitae.com/en/variant-classification/) ([Nykamp et al., Genetics in Medicine, 2017](https://www.ncbi.nlm.nih.gov/pubmed/28492532)). Important attributes of cancer predisposition genes, such as mode of inheritance and mechanism of disease (loss-of-function), have been harvested from [Genomics England PanelApp](https://panelapp.genomicsengland.co.uk/), [Maxwell et al., Am J Hum Genet, 2016](https://www.ncbi.nlm.nih.gov/pubmed/27153395), and [Huang et al., Cell, 2018](https://www.ncbi.nlm.nih.gov/pubmed/29625052)
 
-The ACMG criteria listed in the table below form the basis for the <b>CPSR_CLASSIFICATION</b> implemented in CPSR. Specifically, the <i>score</i> column indicates how much each evidence item contribute to either of the two pathogenicity poles (positive values indicate pathogenic support, negative values indicate benign support). Evidence score along each pole ('B' and 'P') are aggregated, and if there is conflicting or little evidence it will be classified as a VUS. The contribution of ACMG evidence items pr. variant can be seen in the <b>CPSR_CLASSIFICATION_CODE</b> and <b>CPSR_CLASSIFICATION_DOC</b> variables.
+The ACMG/AMP criteria listed in the table below form the basis for the <b>CPSR_CLASSIFICATION</b> implemented in CPSR. Specifically, the <i>score</i> column indicates how much each evidence item contribute to either of the two pathogenicity poles (positive values indicate pathogenic support, negative values indicate benign support). Evidence score along each pole ('B' and 'P') are aggregated, and if there is conflicting or little evidence it will be classified as a VUS. The contribution of ACMG/AMP evidence items pr. variant can be seen in the <b>CPSR_CLASSIFICATION_CODE</b> and <b>CPSR_CLASSIFICATION_DOC</b> variables.
 <br><br>
 
 #### Calibration of classification thresholds 

inst/templates/quarto/cpsr_summary.qmd

@@ -142,6 +142,7 @@ bslib::layout_column_wrap(
   )
 )
 ```
+<b>
 
 ### Variant statistics 
 
@@ -162,4 +163,4 @@ Variant numbers in the targeted cancer predisposition genes (n = `r NROW(primary
 * Number of InDels: __`r cps_report[['content']][['snv_indel']][['v_stat_cpg']][['n_indel']]`__
 * Number of protein-coding variants: __`r cps_report[['content']][['snv_indel']][['v_stat_cpg']][['n_coding']]`__
 
-<br><br>
+<br>

vignettes/output.Rmd

@@ -34,7 +34,7 @@ The report is structured in multiple sections, described briefly below:
         - See section below for [details of biomarker annotations](#biomarker-annotations)
 
   5. __Secondary findings__
-     * Pathogenic variants in the [ACMG recommended list of genes for report of secondary/incidental findings](https://www.ncbi.nlm.nih.gov/clinvar/docs/acmg/)
+     * Pathogenic variants in the [ACMG-recommended list of genes for report of secondary/incidental findings](https://www.ncbi.nlm.nih.gov/clinvar/docs/acmg/)
 
   6. __GWAS hits__
      * Status of relatively common, low-risk variants found in genome-wide association studies of cancer phenotypes (NHGRI-EBI Catalog)